The composition of the oral microbiome in healthy individuals is complex and dynamic, and depends on many factors, such as anatomical location in the oral cavity, diet, oral hygiene habits or host immune responses. It is estimated at present that worldwide about 2 billion people suffer from diseases of the oral cavity, mainly periodontal disease and dental caries. Importantly, the oral microflora involved in local infections may spread and cause systemic, even life-threatening infections. In search for etiological agents of infections in dentistry, traditional approaches are not sufficient, as about 50% of oral bacteria are not cultivable. Instead, metagenomic analyses are particularly useful for studies of the complex oral microbiome – both in healthy individuals, and in patients with oral and dental diseases. In this paper we review the current and future applications of metagenomic studies in evaluation of both the composition of the oral microbiome as well as its potential pathogenic role in infections in dentistry.